Context: The efficacy of treatments for pediatric obesity remains unclear. Objective: We performed a systematic review of randomized trials to estimate the efficacy of nonsurgical interventions for pediatric obesity. Data Sources: Librarian-designed search strategies of nine electronic databases from inception until February 2006, review of reference lists from published reviews, and content expert advice provided potentially eligible studies. Study Selection: Eligible studies were randomized trials of overweight children and adolescents assessing the effect of nonsurgical interventions on obesity outcomes. Data Extraction: Independently and in duplicate, reviewers assessed the quality of each trial and collected data on interventions and outcomes. Data Synthesis: Of 76 eligible trials, 61 had complete data for meta-analysis. Short-term medications were effective, including sibutramine [random-effects pooled estimate of body mass index (BMI) loss of 2.4 kg/m2 with a 95% confidence interval (CI) of 1.8-3.1; proportion of between-study inconsistency not due to chance (I2) = 30%] and orlistat (BMI loss = 0.7 kg/m 2; CI = 0.3-1.2; I2 = 0%). Trials that measured the effect of physical activity on adiposity (i.e. percent body fat and fat-free mass) found a moderate treatment effect (effect size = -0.52; CI = -0.73 to -0.30; I2 = 0%), whereas trials measuring the effect on BMI found no significant effect (effect size = -0.02; CI = -0.21 to 0.18; I2 = 0%), but reporting bias may explain this finding. Combined lifestyle interventions (24 trials) led to small changes in BMI. Conclusions: Limited evidence supports the short-term efficacy of medications and lifestyle interventions. The long-term efficacy and safety of pediatric obesity treatments remain unclear. Copyright © 2008 by The Endocrine Society.